• MAESTRO-NAFLD-1 late-breaker and three other Madrigal abstracts accepted for oral presentation at the EASL International Liver Congress™
• Data from the Phase 3 MAESTRO-NAFLD-1 study continue to reinforce the safety and efficacy profiles of resmetirom
• Madrigal remains on track to disclose topline data from MAESTRO-NASH in the fourth quarter and anticipates filing for accelerated approval under Subpart H next year
• Planned MAESTRO-NASH Outcomes trial, a non-invasive Phase 3 study designed to accelerate the full approval timeline for non-cirrhotic NASH, will evaluate resmetirom effects on liver decompensation events in patients with early NASH cirrhosis
• Madrigal enters into term loan facility with ability to draw up to $250 million to support expansion of clinical development program and preparation for a potential U.S. launch of resmetirom

Company to host conference call at 8:00 AM ET, May 9th, 2022

CONSHOHOCKEN, Pa., May 09, 2022 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for non-alcoholic steatohepatitis (NASH), today announced acceptance of four abstracts for oral presentation at the European Association for the Study of the Liver’s (EASL) International Liver Congress, including a late-breaker presentation of data from the Phase 3 MAESTRO-NAFLD-1 trial, as well as other resmetirom clinical development program updates. The Company also reported financial results for the first quarter of 2022, including the completion of a $250 million term loan facility to support resmetirom clinical and commercial development objectives and position Madrigal for a potential first-to-market launch in NASH. The company drew $50 million from the facility at closing and has the ability to draw a further $200 million under the agreement.

Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, “The MAESTRO-NAFLD-1 data as described below have reinforced our confidence in the safety and potential efficacy of resmetirom in treating non-cirrhotic NASH with significant fibrosis. We look forward to sharing detailed MAESTRO-NAFLD-1 results in a late-breaking presentation at EASL followed by topline results from the MAESTRO-NASH biopsy study in Q4. Based on the totality of efficacy data generated thus far in our clinical development program, we believe resmetirom can both address the underlying drivers of NASH in the liver and also reduce the level of fibrosis that is associated with progression to more advanced disease.”

Dr. Friedman added, “The term loan facility we are announcing today strengthens Madrigal’s balance sheet, providing an additional source of funding that can be drawn at the appropriate times to meet our operational needs and support our strategic priorities, including a new MAESTRO study and the ramp-up for the potential launch of resmetirom in the U.S.”

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "We are planning to expand our NASH development program by initiating a second study in the next few months to complement the clinical outcomes portion of MAESTRO-NASH; this second study, MAESTRO-NASH Outcomes, will non-invasively examine liver-related outcomes (decompensation events) in patients with early NASH cirrhosis. In contrast, MAESTRO-NASH relies primarily on serial liver biopsy to measure progression to cirrhosis. Resmetirom has been studied in over 180 patients with well-compensated NASH cirrhosis in an open-label arm of MAESTRO-NAFLD-1. The safety and efficacy results that will be presented at EASL are supportive of a potential for benefit in this population. A positive outcome in this study, in a group of patients with the highest unmet need, has the potential to significantly broaden the label for resmetirom and increase the commercial opportunity. Furthermore, it is expected to accelerate the path to full approval and enhance the statistical power to assess benefit in patients with non-cirrhotic NASH. The addition of MAESTRO-NASH Outcomes does not alter our timeline for the subpart H NDA submission in non-cirrhotic NASH that is based on the results of the liver biopsy portion of MAESTRO-NASH.”

Dr. Taub added, "As we have continued to gain confidence that we will achieve both the NASH resolution as well as the fibrosis improvement endpoints in the MAESTRO-NASH biopsy study we are moving one point fibrosis reduction up the hierarchy to a primary endpoint along with NASH resolution. While we expect to achieve both endpoints, dual primaries allow for a successful outcome of the study that can be filed for subpart H approval if either the NASH resolution or one point fibrosis reduction liver biopsy endpoint is met.”

Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies commented, “There is an urgent need for NASH treatments that can prevent progression to hepatic decompensation in patients at the early stages of NASH cirrhosis, but few late-stage development programs have focused on this population. The MAESTRO-NASH Outcomes study will help us determine if resmetirom can benefit patients with more advanced disease and achieve the endpoints that are valued most by healthcare providers, regulators, payers and, most importantly, patients.”

Clinical Program Updates

Late-Breaking Presentation and Multiple Oral Presentations at EASLMultiple resmetirom abstracts have been accepted at EASL’s International Liver Congress taking place June 22-26 in London:

• Late-breaking presentation: “Primary data analyses of MAESTRO-NAFLD-1, a 52 week double-blind placebo-controlled phase 3 clinical trial of resmetirom in patients with NAFLD” [Saturday, June 25 at 3:00 PM. Presenter: Stephen Harrison]
• Oral presentation: “Impact of resmetirom-mediated reductions in liver volume and steatosis compared with placebo on the quantification of fibrosis using second harmonic generation in a serial liver biopsy study” [Thursday, June 23 at 4:00 PM. Presenter: Dean Tai]
• Oral presentation: “Utility of FIB-4 thresholds to identify patients with at-risk F2-F3 NASH based on screening data from a 2000 patient biopsy confirmed cohort of resmetirom Phase 3 clinical trial, MAESTRO-NASH” [Saturday, June 25 at 9:15 AM. Presenter: Jörn Schattenberg]
• Oral presentation: “Biomarkers, imaging and safety in a well-compensated NASH cirrhotic cohort treated with resmetirom, a thyroid hormone receptor beta agonist, for 52 weeks” [Saturday, June 25 at 5:45 PM. Presenter: Stephen Harrison]
• Poster: “A higher Fibrosis-4 (FIB-4) score is associated with higher healthcare costs and hospitalizations in patients with nonalcoholic steatohepatitis” [Presenter: Elliot Tapper]
• Poster: “Retrospective AI-based measurement of NASH histology (AIM-NASH) analysis of biopsies from Phase 2 study of Resmetirom confirms significant treatment-induced changes in histologic features of non-alcoholic steatohepatitis” [Presenter: Janani Iyer]

Additional Phase 3 MAESTRO-NAFLD-1 DataIn January, Madrigal announced that primary and key secondary endpoints from the double-blind, placebo-controlled, 969-patient MAESTRO-NAFLD-1 safety study were achieved; resmetirom was safe and well-tolerated and provided significant reductions in liver fat, LDL-c and other atherogenic lipids vs. placebo.

Similar to what has been reported for the 100 mg open-label arm, patients in the resmetirom 80 mg and 100 mg double-blind arms achieved reductions in ALT (p=0.002;